Hybrid Enzyme-Polymeric Capsules/Mesoporous Silica Nanodevice for In Situ Cytotoxic Agent Generation

A novel nanocarrier based on functionalized mesoporous silica nanoparticles able to transport a non-toxic pro-drug and the enzyme responsible for its activation is presented. This nanodevice is able to generate in situ cytotoxic species once accumulated in the tumoral cell. Enzymes are sensitive mac...

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Detalles Bibliográficos
Autores: Baeza, Alejandro, Guisasola, Eduardo, Torres Pardo, María De La Almudena, González Calbet, José María, Melen, Gustavo J., Ramírez, Manuel, Vallet Regí, María Dulce Nombre
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/35409
Acceso en línea:https://hdl.handle.net/20.500.14352/35409
Access Level:acceso abierto
Palabra clave:546
615.46
In situ cytotoxic generation
Mesoporous silica nanoparticles
Enzyme nanocapsules
Drug delivery
Prodrug release
Materiales
Química inorgánica (Química)
3312 Tecnología de Materiales
2303 Química Inorgánica
Descripción
Sumario:A novel nanocarrier based on functionalized mesoporous silica nanoparticles able to transport a non-toxic pro-drug and the enzyme responsible for its activation is presented. This nanodevice is able to generate in situ cytotoxic species once accumulated in the tumoral cell. Enzymes are sensitive macromolecules which can suffer denaturalization in biological media due to the presence of proteases or other aggressive agents. Moreover, the direct attachment of enzymes to the silica surface can reduce their activity by conformational changes or active site blockage. For these reasons, in order to create a robust system able to work in living organisms, the enzymes are previously coated with a protective polymeric shell which allows the attachment on the silica surface preserving their activity. The efficacy of this hybrid nanodevice for antitumoral purposes is tested against several human tumoral cells as neuroblastoma and leukemia showing significant efficacy. It converts this device in a promising candidate for further in vivo studies for oncology therapy.